The etiology of male breast cancer has been difficult to investigate, given its relative rarity with an occurrence less than 1% that of female breast cancer. Most previous studies have involved case-control designs, raising questions about the possibility of recall bias. Analyses of individual prospective studies to identify risk factors are difficult given typically small numbers of accrued cases. In an attempt to overcome these limitations and increase statistical power, we initiated the Male Breast Cancer Pooling Project. We have secured international collaborations resulting in the pooling of 21 studies which have provided close to 2,500 cases of this rare malignancy and 52,000 controls. Initial analyses of the data have focused on the roles of anthropometric and hormonal risk factors, as well as effects of alcohol consumption and cigarette smoking. Similar to female breast cancer, results seemed to support a role for hormonal factors in the etiology of male breast cancer, with significant associations found for Klinefelter syndrome, gynecomastia, obesity, diabetes and being fatherless. There was, however, no relations of risk observed with either alcohol consumption or cigarette smoking.
Given the strong support for a role of hormonal factors in male breast cancer, recent efforts have focused on exploring the etiologic role of endogenous hormones. In collaboration with investigators at Laval University in Quebec, 11 estrogens and androgens have been measured by either gas or liquid chromatography in pre-diagnostic samples from 7 of the collaborating cohort investigations. These analyses show a significant relation of risk with increasing estradiol levels. In contract, androgens were not substantially related to risk, nor were ratios of estrogens to androgens. These associations were not confounded or modified by other male breast cancer risk factors, including body mass index.
John T. Casagrande, Rosie Cooke, Marianne Ewertz, Susan M. Gapstur, Mia M. Gaudet, J. Michael Gaziano, Georgios Gkiokas, Pascal Guenel, Brian E. Henderson, Albert Hollenbeck, Ann W. Hsing, Laurence N. Kolonel, Claudine Isaacs, Kenneth C. Johnson, Valerie McCormack, Karin B. Michels, Eva Negri, Hakan Olsson, Dominick Parisi, Eleni Th. Petridou, Malcolm C. Pike, Elio Riboli, Howard D. Sesso, Kirk Snyder, Anthony J. Swerdlow, David B. Thomas, Dimitrios Trichopoulos, Giske Ursin, Piet A. van den Brandt, Stephen K. Van Den Eeden, Elisabete Weiderpass, Walter C. Willett
For more information, contact Michael Cook.